The overall objective of this International Center for Excellence in Malaria Research (ICEMR) in the SE Asia region is to advance knowledge of how national and regional programs to control and eliminate malaria in Papua New Guinea (PNG), Solomon Islands and Vanuatu affect the epidemiology, transmission and pathogenesis/immunity of Plasmodium falciparum and P. vivax. Infection and morbidity in 3 distinct endemic settings which represent a wide spectrum of malaria endemicity (holoendemic in mainland PNG, meso/hypoendemic in East New Britain PNG, and hypoendemic in Western Province, Solomon Islands). A related goal is to build local capacity and infrastructure to monitor, evaluate and guide ongoing and future malaria interventions used by national health authorities in the region. Transmission and Pathogenesis/immunity Research Projects 2 and 3 are integrated with Epidemiology Project 1 that will evaluate in all three endemic sites the changing patterns of malaria infection and disease that result from progressive deployment of similar malaria interventions - free universal long lasting insecticide treated bed nets and rapid evidence based diagnosis of malaria and treatment with artemether-lumefantrine. Research and infrastructure enhancing activities will be served by GCP compliant Database/Biostatistics and Molecular Diagnostics Cores. Unique features of the program include the potential for gaining novel insight into the control of P. vivax relative to P. falciparum given the anticipated greater resilience of the former to control and elimination, improvement of the meager knowledge of anophelines that transmit malaria in this region of SE Asia and the Pacific (primarily An. punctulatus), appreciation of how diminishing transmission affects P. falciparum and P. vivax genetics, and greater understanding of the significance of continuing exposure as a prerequisite for developing and maintaining naturally acquired immunity against malaria and the impact of various interventions on immune-mediated protection. An advantage of an ICEMR in this site Is the opportunity to rapidly transfer research findings to the monitoring, evaluation and implementation goals of national malaria control programs. Synergy among the ICEMR projects and cores and incorporation ICEMR findings into national programs will help answer unresolved key issues related to malaria control and elimination locally and in the SE Asia region.